3-nitropropionic acid derivatives

ABSTRACT

NOVEL 3-NITROPRIPIONIC ACID DERIVATIVES, NAMELY 2-NITROPROPIONAMIDES AND 3-NITROPROPIONANILIDES, POSSES FUNGICIDAL, INSECTICIDAL, VIRICIDAL, AND THE OTHER ACTIVITY.

United States Patent 3,786,092 S-NITROPROPIONIC ACID DERIVATIVESGianluigi Soldafi, Naugatuck, and Allen E. Smith, Bethany, Conn.,assignors to Uniroyal, Inc., New York,

NI) brewing. Filed Apr. 14, 1969, Ser. No. 816,081 Int. Cl. C071: 103/30US. Cl. 260-561 R 23 Claims ABSTRACT OF THE DISCLOSURE Novel3-nitropropionic acid derivatives, namely 3-nitropropionamides and3-nitropropionanilides, possess fungicidal, insecticidal, viricidal, andother activity.

DISCLOSURE wherein R is hydrogen or alkyl; R, is selected from alkyl,cycloalkyl, aryl, aralkyl, and the substituted derivatives thereofwherein the substituent is independently selected from halo, alkyl,alkoxy, haloalkyl, nitro, cyano and dialkylamino. There may be one ormore of such substituents and Where there are two or more, they may bethe same or different members of the foregoing group.

Examples of R are hydrogen and alkyl having 1 to 4 carbon atoms, such asmethyl, ethyl, propyl (nand iso-) and butyl (n-, iso-, secand tert-).

Examples of R are alkyl having from 1 to 10 carbon atoms, such asmethyl, ethyl, propyl, butyl (n-, iso-, sec-, and tert-), and amyl,hexyl, heptyl, nonyl and decyl; cycloalkyl, especially cycloalkyl having5 and 6 ring carbon atoms, i.e. cyclopentyl and cyclohexyl; aryl, suchas phenyl and such polycyclic aryl groups as naphthyl; and aralkyl, suchas benzyl. Examples of the substituents which may be present where R isa substituted radical are chloro, bromo, fiuoro, methyl, ethyl, propyl(nand iso-) butyl (11-, isoand tert-), hexyl, decyl, methoxy,chloromethyl, trichloromethyl, nitro, cyano and dimethylamino.

Specifically, some further examples of R are p-methylbenzyl, pnitrobenzyl, 2,6-diethylpheny1, p-nitrophenyl, p-cyanophenyl,4-chloro-a-naphthyl, m-bromophenyl, 2,4, 6-trichlorophenyl, and2,5,6-trichlorophenyl.

The 3-nitropropionic acid derivatives of this invention are formedreadily in good yields by the reaction of 3- nitropropionylchloride withaliphatic or aromatic amines in suitable anhydrous solvents, such asacetonitrile or ether, for a period of time of two to four hours attemperatures ranging between 0 and 25 C. The 3-nitropropionylchloridereactant is obtained in almost quantitative yield by reacting3-m'tropropionic acid, prepared as described by T. L. Gresham, et al.,Jour. Am. Chem. Soc., 74, 1323-1325 (1952), with an excess of thionylchloride.

3,786,092 Patented Jan. 15, 1974 Illustrative examples of the3-nitropropionic acid derivatives of this invention are:

Number in Table Compound: I below 3-nitr0propionanilide 12-chloro-3-nitropropionanilide 2 3-methyl-3-nitropropionanilide 33,4'-dichloro-3-nitropropionanilide 4 4'-methyl-3-nitropropionanilide 52'-fluoro-3-nitropropionanilide 6 3-chloro-3-nitropropionanilide 74'-chloro-2-nitropropionanilide 8 N-benzyl-3-nitropropionamide 94-methoxy-3-nitropropionani1ide l0 N-(a-naphthyl)-3-nitropropionamide 11-4-fluoro-3-nitropropionanilide 122'-methoXy-5-nitro-3-nitropropionanilide 13 3-nitro-3nitropropionanilide14 4-dimethylamino-3-nitropropionanilide 15 3 (a,ot, x, trifiuoromethyl)3-nitro-propionanilide 16 2-ch1oro-4'-nitro-3-nitropropionanilide 172',4-dimethyl-3-nitropropionanilide 18 4-bromo-3-nitropropionanilide 192'-bromo-3-nitropropionanilide 2O N-cyclohexyl-3-nitropropionamide 212,4-dichloro-3-nitropropionanilide 222'-rnethyl-4-chloro-3-nitropropionanilide 23N,N-(di-n-butyl)-3-nitropropionamide 242,5'-dimethoXy-3-nitropropionanilide 25 2'-methyl-3-nitropropionanilide1 -26 N-methyl-3-nitropropionanilide 27N-(o-chlorobenzyl)-3-nitropropionamide 28N-(p-chlorobenzyl)-3-nitropropiona1nide 292'-methyl-3-chloro-3-nitropropionanilide 303',4-dimethy1-3-nitropropionani1ide 312',5'-dimethyl-3-nitropropionanilide 322',4',5'-trichloro-3-nitropropionanilide 33N,N-diethyl-3-nitropropionamide 34 N-isobutyl-3-nitropropionamide 35N-(n-hexyl)-3-nitropropionamide 36 N-(n-decyl)-3-nitropropionamide 37Syntheses of the 3-nitr'opropionic acid derivatives of this inventionare illustrated by the following examples.

Example I.--3-Nitropropionanilide To a stirred solution of 33.8 g.(0.364 mole) of aniline in 300 ml. of anhydrous ether were added,dropwise and at about 0 C., 25 g. (0.18 mole) of3-nitropropionylchloride. At the end of the addition stirring wascontinued for one hour at room temperature. A precipitate was formed,filtered, washed with water and the residue dried. Additional anilidewas recovered on evaporation of the ethereal liquors. Recrystallizationof the combined crude products from benzene-hexane yielded 26 g. ofwhite crystalline material melting at 87-9 C. Y e

Analysis.-Calcd. for C H N O (percent): C, 55.67; H, 5.19; N, 14.43.Experimental (percent): C, 55.48; H, 5.36; N, 14.08.

Example II.-4-Chloro-3-ni.tropropionanilide 3-nitropropionylchloride (25g., 0.18 mole) was added dropwise to a stirred solution ofp'chloroaniline (46 g.,

0.362 mole) in 400 ml. of anhydrous ether at 10-15 C. After one hour theprecipitate was filtered, slurried in water and the residue collected.Additional product was recovered from the ethereal solution. Thecombined residues (26.5 g.) recrystallized twice from methanol-water andbenzene-hexane gave a white crystalline product melting at 1l78 C.

Analysis.-Calcd. for C H ClN O (percent): C, 47.27; H, 3.97; N, 12.25.Experimental (percent): C, 47.46; H,

Example III.N-isobutyl-3-nitropropionamide To a cold stirred solution ofisobutylamine (26.6 g., 0.362 mole) in 250 ml. of acetonitrile was addeddropwise 3-nitropropionylchloride (25 g., 0.181 mole) dissolved in 25ml. of acetonitrile. The inorganic salt formed was filtered 011, thesolution evaporated and the residue dissolved in benzene. The benzenesolution was washed twice with diluted (1:10) hydrochloric acid, thenwater. The organic layer was dried over magnesium sulfate anddecolorized. Evaporation of the solvent gave 20 g. of tan oil which wasfurther purified by column chromatography.

Analysis.-Calcd. for CqH14N2O3 (percent): N, 16.08.

4 EXAMPLE Iv 'Fungicidal Activity (Early Blight and Bean Rust) (1) Earlyblight (Alternarz'a solani) test: One gram of 5 the chemical to betested Was ground with three ml. of acetone and 50 mg. of a non-ionicsurface-active agent (Triton X-100 The acetone and surface-active agentare known to be inactive in the biological tests run. The mixture wasdiluted with water, giving suspensions containing 500 and 2000 ppm. ofthe chemical. These suspensions were sprayed on duplicate six inchtomato plants (variety Clarks Early Special) using a gun-type sprayerwhich delivered 2.5 ml. per second. The plants were then placed in thegreenhouse, together with untreated check plants. Twenty-four hourslater the treated and untreated check plants were inoculated with asuspension of Alternaria solani spores by means of a second spray froman atomizer sprayer (delivery rate 1 ml. per second). The plants werethen kept overnight in a controlled 20 chamber at a temperature of 75 F.and 100% relative humidity. In the morning the plants were transferredto the greenhouse. Three days later the disease was scored by comparingthe number of disease lesions of the treated plants with the untreatedcheck plants.

Experimental (percent): N, 15.87-16.07. The formula to determine percentcontrol is:

Infrared spectra of all the 3-nitroprop1onamides m which R was H showedNH amide absorption at M 2.9-- 3.0 All showed absorption at 6.45-6.5 forthe nitro 10 A lesions on treated plant X100 group Avg. no. lesions onuntreated plant The following table sets forth many of the novel comt t1 pounds which are within the invention. pemen con to TABLE I iOgNCHzCHaCN Analysis (percent) of- Calculated Ex erimental R1 (R ishydrogen p Compound unless otherwise indicated) M.P./B.P. Formula C H NC H N Pheny 879 CnHmNlOs 55.67 5.10 14.43 55.48 5.36 14.08o-Chlorophenyl 00-1 CgHnClNgOa 47.27 3.07 12.25 47.88 3.81 12.05 m-Toiyl83-5 CmHnNzOa 57.60 5.81 13. 57.57 5.62 13. 02 3,4-dichlorophenyl. 107-0CQHaClzNiOa 41.05 3.07 10. 65 40.85 3.15 10.73 p-Tolyl 130-2010111110203 57.60 5. 81 13. 45 57.03 5.83 13.53 o-FluorophenyL 89-91"C9HFN105 m-Chlorophenyl 128- C H ClNzOa p-Chlorophenyl 117-8 CQHQCINQOQ,47.27 3.07 12. 25 47.46 3.03 12.06 Benzyl 110-2 ClOHflNiOS 57.60 5. 8113. 45 57.66 5.75 13.11 p-Metlloxyphenyl 107-0 ClOHflNflOl 53.57 5.3012.40 53.35 4.52 12.13 a-naphthyl 121-2 Cl3Hl2N103 63.93 4.05 11.4763.27 5.15 11.38 p-Fluorophenyl 94-5 cqHoFNnog 2-methoxy5-nitrophenyl15960 CwHnNaO 44.62 4.12 15.61 44.70 420 15.01 a-nitrophenyl 128-9"COHDN305 45.10 3.70 17.57 45.82 4.00 17.26 p-Dimethylaminophenyl. 15961a,a,a-trifluoro-mtolyl 93-5 2-chloro-4-nitrophenyL- 124-5 CBHBOlNttOE38.63 2.05 15.36 40.30 2.80 15.10 2,4-xylyl 110-2 p-Bromophenyl. 132-3CQHQBINIOQ 39.58 3.32 10.26 39.47 3.37 10. 26 o-Bromophenyl- 88-88. 5comm-N103 30.58 3.32 10.26 30.81 3.36 10.30 Cyclohexyl 89912,4-dichlorophenyl- 13 ctHtonmoa 41.05 3.07 10.65 41.32 2.83 10.474-chloro-o-tol 121-2 CmHgClNzO; 49.48 4.57 11.54 40.28 4.50 11.25n-Butyl; (R=n-Buty 84 011132110103 12.16 12.11-12.252,5-dimethoxypl1enyl 132F3 CuHuNzOs 51.07 5 11.02 52.27 5 11. o-Tol102-1025" 01611010501 57.60 5 81 13.45 58.27 5 81 13.

- CroHuNaOa 13. 45 13. 19-13. 43

CmH OlNzOa 40.48 4. 57 11.54 40. 62 4. 78 11.1 C uH11C1N2O3 40. 48 4 5711.54 40. 38 4. 63 11. 16

011111410203 50. 45 6. 12. 60 50. 06 6. 37 12.65 OuHuNzOz 50.45 6. 60.006.32 0.111o14N5O3 36. 33 2. 0 42 36.00 2 50 .24 C1H14N20a 16.0816.87-16.90 35 i-Butyl C1H14N2Oa 16. 08 15. 87-16. 07 36 n-HexylCvHrsNzOa 13.85 14.10-14.40 37 n-Decyl 624 CraHzoNaOa 10. 84 11.21

1 2 mm. decomposition. 9 Decomposition.

5 have shown fungicidal, insecticidal, viricidal and other biologicalactivity, as shown by the following examples.

Checks: acetone and surface-active agent solution.

(2) Bean rust (Uromyces phaseoli) evaluation: Two

1 Octyl phenoxy polyethoxy ethanol.

hundred milligrams of the chemical to be tested were dissolved in ml. ofacetone and 60 mg. of a surfactant such as Triton X--100. Thispreparation was diluted with 80 ml. distilled water giving a chemicalsuspension of 2000 p.p.m. 500'p.p.m. suspensions were also prepared. Thechemical suspensions were sprayed on duplicate pots, each containing twosnapbean plants which had, 48 hours prior to this, been inoculated withbean rust Uromyces phaseoli typz'ca Arth. The spray application was madewith a gun-type sprayer delivering 2.5 ml. per second. At the time ofthe chemical spray the bean plants had just begun to expand their firsttrifoliate leaves. The test plants were then placed in a control chamberfor 24 hours at 75 F. and 100% relative humidity. After this time theplants were returned to the greenhouse. About 10 days later the plantswere scored for disease control.

The formula to determine percent control is:

Avg. no. lesions on treated plant 100- (Avg. no. lesions on untreatedplant. 100

=percent control Checks: acetone and Triton X-100 solution.

Early blight, percent control Bean rust Compound No. in 2, 000 500 2,000 500 Table I p.p.m. p.p.m. p.p.m. p.p.m.

EXAMPLE V Insecticidal activity Mosquito larvae test (A edes Aegypti 4thinstar lar- 'vae).-The compound to be tested (10 mg.) is added to 1 ml.analytical reagent grade acetone and 100 ml. water to give a 100 p.p.m.solution, a 25 ml. aliquot of which was added to test tubes prior to theintroduction therein of from 10 to 25 larvae. The tubes were maintainedin darkness for 72 hours, at the end of which time the live and deadlarvae were counted and the percent control as percentage killed wasdetermined.

Checks using acetone at 1000 p.p.m. and 1% were con ducted.

The compounds of the invention also exhibit insecticidal activity withrespect to Mexican bean beetle larvae.

EXAMPLE VI Viricidal activity Viricide test: Southern bean mosaic virusdisease.-- Pinto bean plants were inoculated with a virus preparationcontaining .01 g./ml. silicon carbide for minute wounding l Octylphenoxy polyethoxy ethanol.

Percent control Compound p.p.m. p.p.m.

The chemicals also may he sprayed on cotyledonary leaves in the form ofan aqueous solution containing 2% of a solvent for the chemical and anemulsifier, Triton X-100.

Additionally, certain of the compounds of the invention especially thehalogenated 3 nitropropionanilides, e.g. Compounds 8 and 19, show plantgrowth regulant properties by reducing terminal bud growth andstimulating axillary and growth on cowpeas, Black Valentine beans andapple seedlings.

The preferred compounds of the invention are the halogenated3-nitropropionanilides (e.g., Compounds 2, 4, 9, 12, 19 and 33); thealkylated 3-nitropropionanilides (e.g., Compounds 3 and 18); as well asothers, e.g., Compounds 13, 27 and 36.

It should be apparent to those in the art that the compounds of theinvention, when used in the manner ordinarily employed by those takingadvantage of the aforementioned activities, can and will be used in avariety of ways. Thus the compounds can be admixed with commonly usedwell-known solvents (xylene, iso-butyl alcohol, naphtha, kerosene,mesityl, oxide, etc.), suspension media (especially water) surfactants(non-ionic and ionic surfactants such as alkyl-aryl sulphonates,polyoxyethylene alkylphenols, polyoxyethylated esters of fatty acids,polyoxyethylated alcohols, etc.), carriers, extenders and diluents(talc, clay, attapulgite clay, pyrophyllite (Pyrax ABB) calcium silicate(Microcel E); they also can be combined with other compounds orcommercial preparations which possess like properties, and certainlywith each other; furthermore, these compounds can be applied via soil,seed of foliar treatment, or to locations where fungus, insect or virusactivity is known or expected, and to crops such as cotton, beans, peas,tomatoes, peaches, apples and pears. The commercialization of thecompounds of the invention may take the form of the distribution ofhighly concentrated mixtures of the active compound which are to bediluted or extended by the ultimate consumer prior to use. Typicallysuch concentrates contain the active compound in amounts from 20 to wt.percent of the total composition, the remainder being, e.g., solvent orsuspension medium (e.g. water or other aqueous medium and surfactant,collectively commonly referred to as carrier material).

It is to be understood that those variations of the invention which arewithin the competence of those skilled in the art and which basicallyrely on the teachings described herein are considered to be within thescope of the description and appended claims.

What is claimed is:

1. A compound of the formula:

wherein (a) where R is hydrogen, R, is selected from the groupconsisting of alkyl having from 1 to 10 carbon atoms, cyclohexyl,naphthyl, benzyl, chlorobenzyl, and substituted phenyl having one tothree substituerits wherein up to two substituents are selected fromhalo and up to three substituents are selected from alkyl containing 1to 10 carbon atoms, methoxy, dimethylamino, trifluoromethyl and nitro;or (b) where R is an alkyl group having from 1 to 4 carbon atoms, R isselected from an alkyl group having 1 to 4 carbon atoms, and phenyl.

2. The compound 3',4-dichloro3-nitropropionanilide.

3. The compound N-benzyl-3-nitropropionamide.

4. The compound 2-methyl-4-chloro-3-nitropropionanilide.

5. The compound 2',4'-dimethyl-3-nitropropionani1ide.

6. The compound 2'-methoXy-5'-nitro-3-nitropropionanilide.

7. The compound N-methyl-3-nitropropionanilide.

8. The compound N,N-diethyl-3-nitropropionamide.

9. The compound N-(n-hexyl)-3-nitropropionamide.

10. N-(u-naphthyl)-3-nitropropionamide.

11. 2'-chloro-4'-nitro-3-nitropropionanilide.

12. N-cyclohexyl-3-nitropropionamide.

13. 2',4'-dichloro-3-nitropropionani1ide.

N,N'-(di-n-buty1)-3-nitropropionamide.2',5'-dirnethoxy-3-nitropropionanilide.N-(o-chlorobenzyl)-3-nitropropionamide. N- (p-chlorobenzyl-3-nitropropionamide. 2'-methyl-3'-chloro-3-nitropropionani1ide.3',4-dimethyl-3-nitropropi0nanilide.2',5'-dimethyl-3-nitropropionanilide.2',4',5'-trichloro-3-nitropropionanilide.N-isobutyl-3-nitropropionamide. N-(n-decyl)-3-nitropropionamide.

References Cited Boyd et al.: J. Amer. Chem. Soc., vol. 75, pp. 2762-63(1953). I a

Feuer et 2.1.: J. Org. Chem., vol. 29, pp. 939-40 (1964). Schlesinger etal.: J. Am. Chem. Soc., vol. 78, pp. 6123- 27 (1956). r

Ried et al.: Ann., vol. 631, pp. 185-94 (1960).

20 HARRY I. MOATZ, Primary Examiner US. Cl. X.R.

260562 R, 562 R562 A, 544 Y; 424324

